Have a half dozen mulies down to mine, using 50gr psp bullets and not super hot loads.
Whacked a doe through the ribs, jellied her heart and lungs, and recovered around 38 or so grains of the bullet, up against the off side leg.
Sorta like the sticker I got from an archery shop, and stuck on my bow. "Stay Calm. Pick your Spot!". If you feel the need to take the shot anyways, at a deer that already is running away, in hopes that you can rely on penetration to kill it after you hit it in the arse, it probably is a bad choice...
LOL at the 22 Short comment. Read some reports that the Poachers were killing Elephants with them. They would set up on the trail, and wait for the elephant to step off, which apparently stretched the skin pretty tight, behind the front leg, giving a lung shot.
Not efficient, but certainly effective!